Assuntos
Falso Aneurisma/terapia , Aneurisma Aórtico/terapia , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Procedimentos Endovasculares , Idoso , Falso Aneurisma/diagnóstico por imagem , Falso Aneurisma/etiologia , Aneurisma Aórtico/diagnóstico por imagem , Aneurisma Aórtico/etiologia , Aortografia/métodos , Angiografia por Tomografia Computadorizada , Ecocardiografia Doppler em Cores , Ecocardiografia Transesofagiana , Procedimentos Endovasculares/instrumentação , Evolução Fatal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Dispositivo para Oclusão Septal , Resultado do TratamentoRESUMO
The proliferation of vascular smooth muscle cells is important in the pathogenesis of many vascular diseases. Reactive oxygen species (ROS) produced by NADPH oxidases in smooth muscle cells have been shown to participate in signaling cascades regulating proliferation induced by platelet-derived growth factor (PDGF), a powerful smooth muscle mitogen. We sought to determine the role of Nox5 in the regulation of PDGF-stimulated human aortic smooth muscle cell (HASMC) proliferation. Cultured HASMC were found to express four isoforms of Nox5. When HASMC stimulated with PDGF were pretreated with N-acetyl cysteine (NAC), proliferation was significantly reduced. Proliferation induced by PDGF was also heavily dependent on JAK/STAT activation, as the JAK inhibitor, AG490, was able to completely abolish PDGF-stimulated HASMC growth. Specific knockdown of Nox5 with a siRNA strategy reduced PDGF-induced HASMC ROS production and proliferation. Additionally, siRNA to Nox5 inhibited PDGF-stimulated JAK2 and STAT3 phosphorylation. ROS produced by Nox5 play an important role in PDGF-induced JAK/STAT activation and HASMC proliferation.
